Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML or MDS

NCT04849910 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: VBP101
• Study Type: interventional
• Target: 67
• Locations: 2 countries
• Sites: 15

Brief Summary

This is a Phase 1/2a, multicenter, open-label, first-in-human (FIH) study of VOR33 in participants with AML or MDS who are undergoing human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (HCT).

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Keywords

Leukemia; Acute Myeloid Leukemia; AML; Hematopoietic stem cell transplant; HCT; CD33; Allogeneic; Myelodysplastic Syndromes; Myelodysplastic Syndromes with excess blasts; MDS; MDS-EB; Cell therapy

Outcome Measures

Primary Outcomes (1)

• Incidence of neutrophil engraftment

  Cumulative incidence of patients who achieve neutrophil engraftment (first day of 3 consecutive days of absolute neutrophil count (ANC) ≥500 cells/mm3) by Day 28.

  Day 28

Secondary Outcomes (10)

• Time to neutrophil engraftment

  Up to approximately 28 days

• Time to platelet recovery

  Up to approximately 60 days

• Incidence of acute GVHD Grade (G) G2-G4 and G3-G4

  Up to 24 months

• Incidence of chronic GVHD (all and moderate-severe)

  Up to 24 months

• Incidence of primary and secondary graft failure

  Up to 24 months

Study Arms (3)

Cohort 1

EXPERIMENTAL

VOR33 infusion followed by Mylotarg Dose Level 1

Biological: VOR33; Drug: Mylotarg

Cohort 2

EXPERIMENTAL

VOR33 infusion followed by Mylotarg Dose Level 2

Biological: VOR33; Drug: Mylotarg

Cohort 3

EXPERIMENTAL

VOR33 infusion followed by Mylotarg Dose Level 3

Biological: VOR33; Drug: Mylotarg

Interventions

VOR33 BIOLOGICAL

Allogeneic, human leukocyte antigen (HLA) matched, genome edited hematopoietic stem and progenitor cell (HSPC) therapy product lacking the CD33 myeloid protein

Cohort 1; Cohort 2; Cohort 3

Mylotarg DRUG

Infusion of Mylotarg

Also known as: gemtuzumab ozogamicin

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be ≥18 and ≤70 years of age.
• Patients with AML must have one of the following groups of features that are known to be a risk factor for leukemia relapse:
• BM in morphological remission (\<5% blasts) with adverse-risk disease related genetics at presentation (according to European Leukemia-Net guidelines \[ELN, Döhner 2017\]), or
• Intermediate risk genetics in morphologic remission (\<5% blasts) with other recognized high risk criteria such as MRD+ following therapy, or
• BM with evidence of persistent leukemia 5-10% blasts post induction/salvage therapy. Patients with BM Blast count \>10% may participate with Sponsor Medical Monitor approval. (Note: these patients may have disease-related genetics of any risk criteria at presentation), or
• Any patient in second or greater remission.
• Patients with MDS must have all of the following:
• Previous or current IPSS-R score of High or Very High risk; AND
• Previous or current MDS-IB1 or MDS-IB2 per the 2022 WHO criteria (Khoury 2022)
• AML sample from the patient must have evidence of CD33 expression (\>0%)
• Candidate for HLA-matched allogeneic HCT using a myeloablative conditioning regimen.
• Must have a related or unrelated stem cell donor that is a 8/8 match for HLA-A, -B, -C, and -DRB1.
• Must have adequate performance status and organ function as defined below:
• Performance Status: Karnofsky score of ≥70.
• Cardiac: left ventricular ejection fraction (LVEF) ≥50%

You may not qualify if:

• Prior autologous or allogeneic stem cell transplantation.
• Presence of the following disease-related genetics: t(15; 17)(q22; q21), or t(9; 22)(q34; q11), or other evidence of acute promyelocytic leukemia or chronic myeloid leukemia.
• Prior treatment with Mylotarg™ (gemtuzumab ozogamicin) in the past 3.5 months.
• Active central nervous system (CNS) leukemia.
• Patients diagnosed with Gilbert's syndrome.
• Uncontrolled bacterial, viral, or fungal infections; or known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.

Sponsors & Collaborators

• Vor Biopharma: lead

Study Sites (15)

University of California San Diego Moores Cancer Center

La Jolla, California, 92037, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Winship Cancer Institute Emory University

Atlanta, Georgia, 30322, United States

Location

The University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

National Institutes of Health, Clinical Center

Bethesda, Maryland, 20892, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T2M4, Canada

Location

Related Publications (1)

• Lydeard JR, Lin MI, Ge HG, Halfond A, Wang S, Jones MB, Etchin J, Angelini G, Xavier-Ferrucio J, Lisle J, Salvadore K, Keschner Y, Mager H, Scherer J, Hu J, Mukherjee S, Chakraborty T. Development of a gene edited next-generation hematopoietic cell transplant to enable acute myeloid leukemia treatment by solving off-tumor toxicity. Mol Ther Methods Clin Dev. 2023 Oct 13;31:101135. doi: 10.1016/j.omtm.2023.101135. eCollection 2023 Dec 14.

  PMID: 38027064 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia

Interventions

Gemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: April 19, 2021
• Study Start: December 16, 2021
• Primary Completion: May 28, 2025
• Study Completion: May 28, 2025
• Last Updated: July 29, 2025

Record last verified: 2025-05

Locations

US (14); CA (1)